Defining roles for polysialylation in the early differentiation of human pluripotent stem cells

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Abstract

Glycosylation is a carbohydrate-based post-translational modification attached to proteins and lipids to alter their functional properties and increase structural diversity. The products of this modification, known as glycans, are known to participate in numerous biological processes but their specific roles in human embryonic development have remained elusive. Through this research I have explored the roles of cell surface glycans in the regulation of pluripotency and differentiation of human pluripotent stem cells (hPSCs) as well as identified a novel functional role for the glycan polymer polysialic acid (PSA). Investigation has revealed that polysialylation occurs during the initial differentiation of hESCs to progenitors of all three embryonic germ layers through an enzyme-driven process that is tightly regulated by well-defined developmental networks and is critical for proper differentiation. These findings indicate that glycans are playing active roles during embryonic development and serve to broaden the understanding of developmental glycosylation and the mechanisms driving early cell fate decisions.